Thoracic aortic disease is the fifteenth leading cause of death in the United States, with aortic dissections being the thirteenth leading cause of death for individuals between the ages of 55 and 64 years. The major manifestations of disease affecting the aorta in the thoracic cavity are aneurysms and dissections. The theme of the application, "Specialized Center for Clinically Oriented Research in Thoracic Aortic Aneurysms and Dissections" (SCCOR-TAAD), is to improve our understanding of the pathogenesis of these diseases in hopes of developing better methods to diagnose, treat, and predict outcome of thoracic aortic disease with the ultimate goal of preventing premature deaths. Project 1, Dysregulation of TGF(3 signaling in aortic aneurysms and dissections, Dianna Milewicz, M.D. Ph.D. Project Leader, focuses on elucidating the role that dysregulation of TGF-p signaling plays in both familial and non-familial cases of thoracic aortic aneurysms and dissections. Project 2, Apoptosis of Smooth Muscle Cells in Aortic Aneurysms, Yong-Jian Geng, M.D. Ph.D. Project Leader, addresses accelerated apoptosis of vascular cells as a major pathological change in the development of thoracic aortic aneurysms and dissections. Project 3, Inflammatory Biomarkers of Aortic Aneurysms, Allan Brasier, M.D. Project Leader, focuses on elucidating the role of angiotensin II (Ang II)- induced inflammation in aortic aneurysms. Project 4, Predictors of Outcomes after Acute Aortic Dissection, Chul Ahn, Ph.D., Project Leader, will explore the hypothesis that there are clinical, socioeconomic, genetic, and plasma markers that will predict which individuals will have an adverse outcome after an acute dissection. Project 5, Genetic Determinants of Thoracic Aortic Aneurysms and Dissections, Xing Li Wang, M.D., Ph.D. Project Leader, will explore the hypothesis that genetic variants contribute significantly to sporadic thoracic aortic aneurysms and dissections. Project 6, Computerized Ultrasound/MR Imaging for Thoracic Aortic Aneurysms and Dissections, Jeff Towbin, M.D. Project Leader, is focused on improving the ability to detect aortic disease using ultrasound and MRI. The proposed SCCOR-TAAD has been established to take advantage of the considerable clinical expertise, patient population, research talent and established centers in the Texas Medical Center, and represents a comprehensive research approach to understand the pathology, identify biomarkers that predict progression and outcome, and improve the methods to diagnose thoracic aortic disease.